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Background: Equations to estimate glomerular filtration rate based on serum creatinine are commonly used in cancer patients to assess renal function. However, there is uncertainty regarding which equation is most appropriate for this population and the impact of different creatinine assays., Methods: Measured isotopic glomerular filtration rate results from 120 oncology patients were used to evaluate and compare all four versions of the Wright equation, Cockcroft and Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration and the Janowitz and Williams formula; using eight different creatinine assays (five Jaffe, three enzymatic)., Results: The enzymatic version of the Wright equation without creatine kinase performed better than the other versions for all eight creatinine assays. However, MDRD and Janowitz and Williams gave the best overall performance in this patient population. Performance was highly dependent on the creatinine assay used, for example, the percentage of results within 30% of the isotopic glomerular filtration rate (P30) ranged from 90.8% to 60.8% for MDRD., Conclusion: The performance of any equation to estimate glomerular filtration rate is highly dependent on the creatinine assay used. Oncology units should assess the performance of glomerular filtration rate equations using their laboratory creatinine assay to determine whether they can be used safely and effectively in cancer patients.

Guidelines state that patients undergoing isotope glomerular filtration rate (GFR) tests should maintain adequate hydration, but pragmatically these tests can coincide with procedures requiring the patient not to eat or drink ('nil-by-mouth') for up to 12 hours beforehand. This study investigated the impact of a 12-hour nil-by-mouth regime on GFR measurement. Twelve healthy volunteers were recruited from our institution. Exclusion criteria included diabetes mellitus, being under 18 years of age and pregnancy. Isotope GFR measurements were carried out on these volunteers twice. One of the tests adhered strictly to the British Nuclear Medicine Society (BNMS) guidelines for GFR measurement and the other test was carried out after the volunteers had refrained from eating or drinking anything for 12 hours. The order of these tests was randomly assigned. The results show that after a nil-by-mouth regime, participants' average absolute GFR fell from 108 ml/min to 97 ml/min (p < .01), while normalised GFR fell from 97 ml/min/1.73 m 2 to 88 ml/min/1.73m 2 (p < .01). Serum creatinine rose from 68 mmol/L to 73 mmol/L (p < .05). There were no changes in blood pressure, serum hydration markers or bio-impedance measured fluid status. Urine analysis showed statistically significant increases in urea, creatinine and osmolality levels after the nil-by-mouth regime. The results highlight the importance of following current guidelines recommending fluid intake during the procedure. Practitioners should consider what other outpatient appointments are being scheduled concurrently with a GFR test.

Background: Hyperosmolar infant feeds can cause osmotic diarrhoea and may be a risk factor for necrotising enterocolitis; the osmolality of infant formula is therefore usually <400 mOsm kg(-1) . However, in fluid-restricted infants and those needing nutritional support, formulas may be over-concentrated or supplemented. The present study aimed to determine the effect of these practices on osmolality., Methods: A clinical laboratory osmometer was used to measure the osmolality of infant formulas. The effect of over-concentration and supplementation on osmolality was then determined using three and seven different infant formulas, respectively. Osmolalities were measured in triplicate., Results: The effect of over-concentration was shown to be linear using Pepti Junior (Cow & Gate, Trowbridge, UK) at concentrations of 12.8% (standard), 17% and 19%. This linear relationship was also demonstrated with Enfamil A.R. (Mead Johnson Nutritionals, Uxbridge, UK) (15%) and Neocate (SHS International Ltd, Liverpool, UK) (21%). The effect of individual additives on osmolality was found to be similar for the seven infant formulas. All preparations of SMA High Energy (SMA Nutrition, Maidenhead, UK) and five of the 12 preparations of Nutriprem 1 (Cow & Gate) exceeded an osmolality of 400 mOsm kg(-1) ., Conclusions: The effect of over-concentrating infant formulas was shown to be linear, meaning that the osmolality at different concentrations can be predicted accurately. The over-concentrated infant formulas that were measured in the present study did not exceed 400 mOsm kg(-1) , with the exception of 21% Neocate, which would not be used in practice. When supplemented, some infant formulas exceeded an osmolality of 400 mOsm kg(-1) ; this may be relevant in cases of feed intolerance or in those at risk of necrotising enterocolitis., (© 2012 The Authors Journal of Human Nutrition and Dietetics © 2012 The British Dietetic Association Ltd.)

Background: Timely detection of acute kidney injury (AKI) in hospital patients has been hampered by the multiple definitions of AKI and difficulties applying their criteria. A laboratory delta check may provide an effective means of detecting patients developing AKI. This study compared three of the proposed AKI definitions and a delta check to detect AKI using serum creatinine results of hospital inpatients., Methods: Serum creatinine results for 2822 inpatients were gathered retrospectively from the clinical biochemistry database. All serum creatinine results within 30 d of admission were included for each patient and assessed for AKI according to four criteria: Risk, Injury, Failure (RIFLE), Acute Kidney Injury Network (AKIN), Waikar & Bonventre or a delta check (increase of >26 μmol/L between two successive values)., Results: A total of 149 (11.3%) patients were defined as having AKI by at least one of the four criteria. Different populations of patients were identified by each criterion. The number of patients identified and the incidence of AKI were as follows: RIFLE 94 (7.1%), AKIN 125 (9.5%), Waikar & Bonventre 100 (7.6%) and delta check 146 (11.1%). The delta check detected 132 (98%) of all 135 cases detected by the other three criteria. A further 14 patients were detected solely by the delta check., Conclusions: The different definitions proposed for AKI detect different populations of patients. A laboratory delta check detected 98% of all the patients identified by AKIN, RIFLE and Waikar & Bonventre combined and could therefore provide a practical way of detecting AKI patients.

Although different detergents can give rise to detergent-resistant membranes of different composition, it is unclear whether this represents domain heterogeneity in the original membrane. We compared the mechanism of action of five detergents on supported lipid bilayers composed of equimolar sphingomyelin, cholesterol, and dioleoylphosphatidylcholine imaged by atomic force microscopy, and on raft and nonraft marker proteins in live cells imaged by confocal microscopy. There was a marked correlation between the detergent solubilization of the cell membrane and that of the supported lipid bilayers. In both systems Triton X-100 and CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) distinguished between the nonraft liquid-disordered (l(d)) and raft liquid ordered (l(o)) lipid phases by selectively solubilizing the l(d) phase. A higher concentration of Lubrol was required, and not all the l(d) phase was solubilized. The solubilization by Brij 96 occurred by a two-stage mechanism that initially resulted in the solubilization of some l(d) phase and then progressed to the solubilization of both l(d) and l(o) phases simultaneously. Octyl glucoside simultaneously solubilized both l(o) and l(d) phases. These data show that the mechanism of membrane solubilization is unique to an individual detergent. Our observations have significant implications for using different detergents to isolate membrane rafts from biological systems.

In overhydrated hereditary stomatocytosis (OHSt), the membrane raft-associated stomatin is deficient from the erythrocyte membrane. We have investigated two aspects of raft structure and function in OHSt erythrocytes. First, we have studied the distribution of other membrane and cytoskeletal proteins in rafts by analysis of detergent-resistant membranes (DRMs). In normal erythrocytes, 29% of the actin was DRM-associated, whereas in two unrelated OHSt patients the DRM-associated actin was reduced to <10%. In addition, there was a reduction in the amount of the actin-associated protein tropomodulin in DRMs from these OHSt cells. When stomatin was expressed in Madin-Darby canine kidney cells, actin association with the membrane was increased. Second, we have studied Ca2+-dependent exovesiculation from the erythrocyte membrane. Using atomic force microscopy and proteomics analysis, exovesicles derived from OHSt cells were found to be increased in number and abnormal in size, and contained greatly increased amounts of the raft proteins flotillin-1 and -2 and the calcium binding proteins annexin VII, sorcin and copine 1, while the concentrations of stomatin and annexin V were diminished. Together these observations imply that the stomatin-actin association is important in maintaining the structure and in modulating the function of stomatin-containing membrane rafts in red cells.

Glycosyl-phosphatidylinositol (GPI)-anchored proteins are enriched in cholesterol- and sphingolipid-rich lipid rafts within the membrane. Rafts are known to have roles in cellular organization and function, but little is understood about the factors controlling the distribution of proteins in rafts. We have used atomic force microscopy to directly visualize proteins in supported lipid bilayers composed of equimolar sphingomyelin, dioleoyl-sn-glycero-3-phosphocholine and cholesterol. The transmembrane anchored angiotensin converting enzyme (TM-ACE) was excluded from the liquid ordered raft domains. Replacement of the transmembrane and cytoplasmic domains of TM-ACE with a GPI anchor (GPI-ACE) promoted the association of the protein with rafts in the bilayers formed with brain sphingomyelin (mainly C18:0). Association with the rafts did not occur if the shorter chain egg sphingomyelin (mainly C16:0) was used. The distribution of GPI-anchored proteins in supported lipid bilayers was investigated further using membrane dipeptidase (MDP) whose GPI anchor contains distearoyl phosphatidylinositol. MDP was also excluded from rafts when egg sphingomyelin was used but associated with raft domains formed using brain sphingomyelin. The effect of sphingomyelin chain length on the distribution of GPI-anchored proteins in rafts was verified using synthetic palmitoyl or stearoyl sphingomyelin. Both GPI-ACE and MDP only associated with the longer chain stearoyl sphingomyelin rafts. These data obtained using supported lipid bilayers provide the first direct evidence that the nature of the membrane-anchoring domain influences the association of a protein with lipid rafts and that acyl chain length hydrophobic mismatch influences the distribution of GPI-anchored proteins in rafts.

A focused SAR study around the previously reported selective 5-HT(7) receptor antagonist, SB-269970-A has resulted in the identification of a structurally related analogue having an improved pharmacokinetic profile. Replacement of the phenolic group in SB-269970-A with an indole moiety, and replacement of the piperidinyl 4-methyl group with a heterocyclic ring system proved to be the key changes leading to the identification of SB-656104-A.

Twenty-six patients with severe chronic obstructive lung disease exercised on a treadmill while breathing either room air, supplementary compressed air, or O2. Endurance was significantly increased by O2, but there was no improvement in maximal work rate. No relation was found between increased endurance and the degree of hypoxia, hypercarbia, or acidosis during exercise or the changes in these while breathing O2.